Pan-AKT Inhibitor Capivasertib With Docetaxel and Prednisolone in Metastatic Castration-Resistant Prostate Cancer: A...

Area of Science:

• Oncology
• Pharmacology

Background:

• Capivasertib is a pan-AKT inhibitor with preclinical activity in metastatic castration-resistant prostate cancer (mCRPC).
• Preclinical studies suggested a synergistic effect of capivasertib when combined with docetaxel in mCRPC.

Purpose of the Study:

• To evaluate the efficacy of capivasertib plus docetaxel and prednisolone compared to placebo plus docetaxel and prednisolone in patients with mCRPC.
• To assess the impact of capivasertib on composite progression-free survival (cPFS) and overall survival (OS) in mCRPC.
• To analyze cPFS and OS based on PI3K/AKT/PTEN pathway activation status.

Main Methods:

• A randomized, placebo-controlled phase II trial (ProCAID) enrolled 150 patients with mCRPC.
• Patients received docetaxel and prednisolone, with random assignment to oral capivasertib or placebo.
• The primary endpoint was cPFS, including prostate-specific antigen progression events; OS was a secondary endpoint.

Main Results:

• Median cPFS was similar between the capivasertib and placebo arms (7.03 vs. 6.70 months; HR, 0.92; P = .32).
• Median OS was significantly longer in the capivasertib arm (31.15 vs. 20.27 months; HR, 0.54; P = .01).
• Adverse events were comparable, with diarrhea, fatigue, nausea, and rash being common with capivasertib.

Conclusions:

• Capivasertib addition to docetaxel and prednisolone did not improve cPFS in mCRPC, regardless of pathway activation.
• The observed improvement in OS with capivasertib warrants further investigation and validation in future studies.
• The PI3K/AKT/PTEN pathway activation status did not appear to influence the efficacy outcomes.